Cholesterol is an essential constituent of all animal cell membranes. Cholesterol reduces the permeability of the membrane, increases the membrane's mechanical strength and helps to organize the membrane constituents laterally into domains. In the cell, cholesterol's abundance is tightly controlled through biosynthetic, storage, ingestion, and transfer pathways. Through these pathways, cells have the ability to adjust their cholesterol level to their needs.
Unfortunately, in some instances, in vivo cholesterol levels are not properly adjusted. Cholesterol disorders, specifically high serum levels of cholesterol and the mishandling of cholesterol in cells of arterial walls, may cause disease and death in humans by contributing to the formation of atherosclerotic plaques in arteries throughout the body. In fact, cholesterol disorders in the United States contribute to such a high number of health issues that the National Heart, Lung, and Blood Institute launched the National Cholesterol Education Program in 1985. The goal of the National Cholesterol Education Program is to contribute to reducing illness and death from coronary heart disease in the United States by reducing the percent of Americans with high blood cholesterol. The program plans to do this by raising awareness of the link between high cholesterol levels and coronary heart disease.
Many of the illnesses triggered by cholesterol abnormalities are addressed through both increased education and drug treatment. Current drugs used for treatment of cholesterol related disorders are compounds called statins, which inhibit cholesterol biosynthesis by blocking the production of the cholesterol precursor, mevalonic acid. However, mevalonic acid is used by the body to synthesize many other important cellular constituents. Unfortunately, because of the numerous cellular uses for mevalonic acid, statins, which are largely non-specific, often have side effects because they suppress a variety of metabolic functions other than cholesterol biosynthesis.
Accordingly, there is need to find other therapeutic agents to combat cholesterol disorders as well as methods for identifying such compounds.